Human cancer vaccines

成功地研究了三个研究项目。1)从自体CTL和骨肉瘤OS2000细胞系中鉴定出人骨肉瘤抗原PBF，即人乳头瘤结合因子。PBF在大部分软组织肿瘤和约50%的上皮性肿瘤中表达，而在正常组织中不表达，尤其是在蛋白水平上。这些观察结果表明，PBF可用于肿瘤的免疫治疗。2)肿瘤抗原的反向免疫研究表明Survivin可以作为肿瘤抗原发挥作用。特别是，Survivin衍生的2B多肽以人类白细胞抗原-A24限制性的方式诱导许多癌症患者的CTL。我们目前正在进行这种多肽在结肠癌、乳腺癌和肺癌中的I期临床试验，表明它没有不良反应。其中一些患者表现出一定的临床反应，如CT显示肿瘤体积缩小以及肿瘤标志物水平下降。我们还在进行来自SYT-SSX染色体易位融合产品的人类白细胞抗原-A24限制性B肽在滑膜肉瘤患者中的I期临床试验。在这项试验中，没有不良反应，六名患者中有两名显示四聚体阳性CTL前体细胞数量增加。3)利用生物信息学方法鉴定了35个新的肿瘤抗原。通过RT-PCR分析证实，在35个抗原中有7个与肿瘤抗原具有严格的表达谱。

Three research projects were successfully studied. 1) We identified human osteosarcoma antigen PBF, papilloma-binding factor, from autologous CTL and osteosarcoma OS2000 line. PBF was expressed in a large part of soft part tumors as well as approximately 50 % tumors of epithelial origins, whereas it was not detected in normal part of tissues particularly in the protein level. These observations suggest that PBF could be utilized in the immunotherapy of cancers. 2) Reverse-immunological approaches of tumor antigens indicated that survivin could work as the tumor antigens. Particularly, survivin-derived 2Bpeptide induced CTL in many cancer patients in the HLA-A24 restricted manner. We are now underway the phase I clinical trials of this peptide in colon, breast, lung cancers, indicating that there are no adverse effects. Some of these patients demonstrated certain clinical responses such as reduction in tumor size in CT as well as in tumor marker levels. We are also underway the phase I clinical trials of HLA-A24-restricted B peptide derived from the SYT-SSX chromosomal translocation fusion product in synovial sarcoma patients. In this trial, there are no adverse effects, and two out of six patients indicated an increasing number of tetramer-positive CTL precursors. 3) We identified 35 novel tumor antigens by bioinformatics in silico approaches. Wet studies by using RT-PCR analysis confirmed that 7 out of 35 antigens have strict expression profiles as the tumor antigens.